PD-L1 status by immunohistochemistry (IHC) is prognostic in metastatic renal cell carcinoma (mRCC) and its role as a potential predictive biomarker is under investigation. Using tumor tissue from the METEOR (NCT01865747) and CABOSUN (NCT01835158) clinical trials, we explored whether PD-L1 expression and the extent of the immune cell infiltrate can serve as prognostic and/or predictive biomarkers for cabozantinib and other targeted agents.
IHC double-staining for PD-L1 and CD45/CD163 (immune cell markers) was performed on tumor tissue from METEOR(n=306) and CABOSUN(n=110) clinical trials. Immune cell density and MET expression levels were also analyzed. Our primary aim was to correlate progression-free survival (PFS) by independent central review with PD-L1 status in patients treated with cabozantinib, everolimus (METEOR) or sunitinib (CABOSUN). Overall survival (OS) was also interrogated.
TC PD-L1 expression (≥1% cutoff) was detected in 29% and 23% of tumors from patients in the METEOR and CABOSUN trials, respectively. On univariate analysis, patients with PD-L1-positive TC had poorer PFS and OS than patients with PD-L1-negative TC on both trials, independent of therapy. On multivariable analysis and when combining the two trials, the association between TC PD-L1 expression and OS was statistically significant for all patients (p=0.034) and for patients treated on cabozantinib only (p=0.038). Cabozantinib was associated with improved PFS (HR<0.70) and OS (HR<0.85) compared to everolimus and sunitinib irrespective of PD-L1 expression.
Higher PD-L1 expression results in worse clinical outcomes in mRCC treated with targeted therapy. Furthermore, PD-L1 expression is not predictive of response to cabozantinib therapy.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2019 Aug 01 [Epub ahead of print]
Abdallah Flaifel, Wanling Xie, David A Braun, Miriam Ficial, Ziad Bakouny, Amin H Nassar, Rebecca B Jennings, Bernard Escudier, Daniel J George, Robert J Motzer, Michael J Morris, Thomas Powles, Evelyn Wang, Ying Huang, Gordon J Freeman, Toni K Choueiri, Sabina Signoretti
Pathology, Brigham and Women’s Hospital., Biostatistics and Computational Biology, Dana-Farber Cancer Institute., Medical Oncology, Dana-Farber Cancer Institute., Medicine, Brigham and Women’s Hospital., Department of Pathology, Brigham and Women’s Hospital., Gustave-Roussy., Departments of Medicine and Surgery, Duke University, Duke Cancer Institute., Department of Medicine, Memorial Sloan Kettering Cancer Center., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College., Experimental Cancer Medicine Centre, Queen Mary University of London., Translational Medicine, Exelixis, Inc., Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute., Department of Medical Oncology, Dana-Farber Cancer Institute., Dana-Farber Cancer Institute, Harvard Medical School., Department of Pathology, Brigham and Women’s Hospital .